Do You Know... Methadone
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Effect of Intranasal Ketamine Vs Fentanyl on Pain
1 PROTOCOL SYNOPSIS 2 STUDY TITLE: 3 Pain Reduction with Intranasal Medications for Extremity Injuries (PRIME): A Randomized Clinical 4 Noninferiority Trial of Intranasal Ketamine vs. Fentanyl 5 6 PROTOCOL TITLE 7 Pain Reduction with Intranasal Medications for Extremity injuries (PRIME) 8 9 PRINCIPAL INVESTIGATOR: 10 Theresa M. Frey, MD 11 Assistant Professor Clinical Pediatrics 12 Division of Pediatric Emergency Medicine 13 Cincinnati Children’s Hospital Medical Center 14 513-636-7966 15 [email protected] 16 17 CO-INVESTIGATORS: 18 Matthew R. Mittiga, MD 19 Todd A. Florin, MD, MSCE 20 Michelle C. Caruso, PharmD, BCPS 21 Nanhua Zhang, PhD 22 Yin Zhang, MS 23 24 I. ABSTRACT 25 26 Introduction: Inadequate pain control in the emergency department, particularly in the pediatric 27 population, is a major health concern. The intranasal route of medication administration is gaining 28 popularity secondary to its rapid onset of action, minimal discomfort for the patient and relative 29 simplicity. When pediatric patients present with moderate to severe pain from traumatic injuries, 30 opioids are currently the most frequently used class of analgesia, but they may not always be the best 31 option for numerous reasons. Sub-dissociative dosing of ketamine has been shown to be an effective 32 alternative to opioids in providing adequate pain relief. 33 34 Objectives: The objectives of this study are to 1) determine if intranasal ketamine is non-inferior to 35 intranasal fentanyl in reduction of pain in children presenting with extremity injuries and 2) define and 36 compare the level of sedation and respiratory side effect profile associated with intranasal ketamine and 37 fentanyl. -
Biased Versus Partial Agonism in the Search for Safer Opioid Analgesics
molecules Review Biased versus Partial Agonism in the Search for Safer Opioid Analgesics Joaquim Azevedo Neto 1 , Anna Costanzini 2 , Roberto De Giorgio 2 , David G. Lambert 3 , Chiara Ruzza 1,4,* and Girolamo Calò 1 1 Department of Biomedical and Specialty Surgical Sciences, Section of Pharmacology, University of Ferrara, 44121 Ferrara, Italy; [email protected] (J.A.N.); [email protected] (G.C.) 2 Department of Morphology, Surgery, Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy; [email protected] (A.C.); [email protected] (R.D.G.) 3 Department of Cardiovascular Sciences, Anesthesia, Critical Care and Pain Management, University of Leicester, Leicester LE1 7RH, UK; [email protected] 4 Technopole of Ferrara, LTTA Laboratory for Advanced Therapies, 44122 Ferrara, Italy * Correspondence: [email protected] Academic Editor: Helmut Schmidhammer Received: 23 July 2020; Accepted: 23 August 2020; Published: 25 August 2020 Abstract: Opioids such as morphine—acting at the mu opioid receptor—are the mainstay for treatment of moderate to severe pain and have good efficacy in these indications. However, these drugs produce a plethora of unwanted adverse effects including respiratory depression, constipation, immune suppression and with prolonged treatment, tolerance, dependence and abuse liability. Studies in β-arrestin 2 gene knockout (βarr2( / )) animals indicate that morphine analgesia is potentiated − − while side effects are reduced, suggesting that drugs biased away from arrestin may manifest with a reduced-side-effect profile. However, there is controversy in this area with improvement of morphine-induced constipation and reduced respiratory effects in βarr2( / ) mice. Moreover, − − studies performed with mice genetically engineered with G-protein-biased mu receptors suggested increased sensitivity of these animals to both analgesic actions and side effects of opioid drugs. -
Fact Sheet on Methadone
Fact Sheet: Methadone Common Questions about Methadone • What is the typical dose of methadone and how is it taken? • How does someone know methadone is working? • How long does a person take methadone? • Who can prescribe methadone? • Can a person overdose on methadone? What is the typical dose of methadone and how is it taken? • Due to methadone’s slow and steady activation of opioid receptors, a person requires only one methadone dose per day. • Every person is different, and dosing should be individualized, based on a person’s experience of a reduction of withdrawal symptoms and cravings. • Most people start with an initial dose of 30-35 mg. It is then increased by 5mg every 3 days until a person experiences a relief from withdrawal symptoms.1 • Methadone is taken by mouth in a liquid form. • The recommended therapeutic (i.e., effective) dose of methadone is between 60 and 120 mg.1 How does someone know methadone is working? • The person will stop feeling withdrawal symptoms. • The person will also experience fewer cravings to use opioids. The intensity of their cravings will go down, but they may not completely go away.1 o Someone taking methadone may still have cravings to use other substances such as cocaine, benzodiazepines, alcohol, etc. The 3 Dimensions of Cravings: Frequency Duration Severity Number of separate times Once a craving starts, it Cravings range in a person starts to can range in how long it intensity, such as how experience a craving lasts at a high, distracting overwhelming, distracting, during the day. level. This could be and painful they feel. -
Methadone Hydrochloride Tablets, USP) 5 Mg, 10 Mg Rx Only
ROXANE LABORATORIES, INC. Columbus, OH 43216 DOLOPHINE® HYDROCHLORIDE CII (Methadone Hydrochloride Tablets, USP) 5 mg, 10 mg Rx Only Deaths, cardiac and respiratory, have been reported during initiation and conversion of pain patients to methadone treatment from treatment with other opioid agonists. It is critical to understand the pharmacokinetics of methadone when converting patients from other opioids (see DOSAGE AND ADMINISTRATION). Particular vigilance is necessary during treatment initiation, during conversion from one opioid to another, and during dose titration. Respiratory depression is the chief hazard associated with methadone hydrochloride administration. Methadone's peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects, particularly in the early dosing period. These characteristics can contribute to cases of iatrogenic overdose, particularly during treatment initiation and dose titration. In addition, cases of QT interval prolongation and serious arrhythmia (torsades de pointes) have been observed during treatment with methadone. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Methadone treatment for analgesic therapy in patients with acute or chronic pain should only be initiated if the potential analgesic or palliative care benefit of treatment with methadone is considered and outweighs the risks. Conditions For Distribution And Use Of Methadone Products For The Treatment Of Opioid Addiction Code of Federal Regulations, Title 42, Sec 8 Methadone products when used for the treatment of opioid addiction in detoxification or maintenance programs, shall be dispensed only by opioid treatment programs (and agencies, practitioners or institutions by formal agreement with the program sponsor) certified by the Substance Abuse and Mental Health Services Administration and approved by the designated state authority. -
Guidelines for Ketamine Use
St Joseph's Mercy Hospice Auckland NZ Guidelines for Ketamine Use Ketamine is a dissociative anaesthetic agent which has analgesic properties in sub- anaesthetic doses 1 Its principal site of action is in the dorsal horn of the spinal cord where it blocks the N-methyl D-aspartate (NMDA) receptor complex. Ketamine is used in palliative care settings primarily for neuropathic pain which is unresponsive or poorly responsive to first-line analgesics (which may include one or more of opioid drug, NSAID, tricyclic antidepressant, or anticonvusant) It has also been used for phantom limb and ischaemic pain and for intractable incident pain or prior to procedures such as dressing changes. Potential side effects Ketamine Routine use of ketamine is limited by its cost and potential side effects which may occur in up to 40% of patients; These may include: Psychotomimetic phenomena – “feeling strange” - dysphoria, vivid dreams, nightmares, hallucinations, altered body image. These effects may be minimised or treated by concurrent use of haloperidol or a benzodiazepine Delirium Hypertension, tachycardia Diplopia, nystagmus Erythema and pain at injection site Contraindications to ketamine use Ketamine has the potential to increase intra-cranial and intra-ocular pressures. It is contraindicated in patients with a history of hypertension, cerebrovascular disease or epilepsy and should be used with caution in patients with raised intra-cranial pressure and/or known cerebral metastases. Dosage regimens for Ketamine use 1. “Burst ketamine” 2 Ketamine is prescribed as a ‘burst’or ‘pulse’ course for a maximum of 5 days. The dose is titrated up, in a stepwise fashion, and once the lowest effective dose is achieved it is continued for 3 days at that dose then stopped. -
Methadone and the Anti-Medication Bias in Addiction Treatment
White, W. & Coon, B. (2003). Methadone and the anti-medication bias in addiction treatment. Counselor 4(5): 58-63. Methadone and the Anti-medication Bias in Addiction Treatment William L. White, MA and Brian F. Coon, MA, CADC An Introductory Note: This article is long overdue. Like many addiction counselors personally and professionally rooted in the therapeutic community and Minnesota model programs of the 1960s and 1970s, I exhibited a rabid animosity toward methadone and protected these beliefs in a shell of blissful ignorance. That began to change in the late 1970s when a new mentor, Dr. Ed Senay, gently suggested that the great passion I expressed on the subject of methadone seemed to be in inverse proportion to my knowledge about methadone. I hope this article will serve as a form of amends for that ignorance and arrogance. (WLW) There is a deeply entrenched anti-medication bias within the field of addiction treatment. This bias is historically rooted in the iatrogenic insults that have resulted from attempts to treat drug addiction with drugs. The most notorious of these professional practices includes: coaching alcoholics to substitute wine and beer for distilled spirits, treating alcoholism and morphine addiction with cocaine and cannabis, switching alcoholics from alcohol to morphine, failing repeatedly to find an alcoholism vaccine, employing aversive agents that linked alcohol or morphine to the experience of suffocation and treating alcoholism with drugs that later emerged as problems in their own right, e.g., barbiturates, amphetamines, tranquilizers, and LSD. A history of harm done in the name of good culturally and professionally imbedded a deep distrust of drugs in the treatment of alcohol and other drug addiction (White, 1998). -
(Methadone Hydrochloride Oral Concentrate USP) and Methadose
NDA 17-116/S-021 Page 3 Methadose™ Oral Concentrate (methadone hydrochloride oral concentrate USP) and Methadose™ Sugar-Free Oral Concentrate (methadone hydrochloride oral concentrate USP) dye-free, sugar-free, unflavored CII Rx only FOR ORAL USE ONLY Deaths have been reported during initiation of methadone treatment for opioid dependence. In some cases, drug interactions with other drugs, both licit and illicit, have been suspected. However, in other cases, deaths appear to have occurred due to the respiratory or cardiac effects of methadone and too-rapid titration without appreciation for the accumulation of methadone over time. It is critical to understand the pharmacokinetics of methadone and to exercise vigilance during treatment initiation and dose titration (see DOSAGE AND ADMINISTRATION). Patients must also be strongly cautioned against self- medicating with CNS depressants during initiation of methadone treatment. Respiratory depression is the chief hazard associated with methadone hydrochloride administration. Methadone's peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects, particularly in the early dosing period. These characteristics can contribute to cases of iatrogenic overdose, particularly during treatment initiation and dose titration. Cases of QT interval prolongation and serious arrhythmia (torsades de pointes) have been observed during treatment with methadone. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, NDA -
Hydromorphone
Hydromorphone WHAT IS HYDROMORPHONE? sedation, and reduced anxiety. It may also cause Hydromorphone belongs to a class of drugs mental clouding, changes in mood, nervousness, called “opioids,” which includes morphine. It and restlessness. It works centrally (in the has an analgesic potency of two to eight times brain) to reduce pain and suppress cough. greater than that of morphine and has a rapid Hydromorphone use is associated with both onset of action. physiological and psychological dependence. WHAT IS ITS ORIGIN? What is its effect on the body? Hydromorphone is legally manufactured and Hydromorphone may cause: distributed in the United States. However, • Constipation, pupillary constriction, urinary retention, users can obtain hydromorphone from nausea, vomiting, respiratory depression, dizziness, forged prescriptions, “doctor-shopping,” impaired coordination, loss of appetite, rash, slow or theft from pharmacies, and from friends and rapid heartbeat, and changes in blood pressure acquaintances. What are its overdose effects? What are the street names? Acute overdose of hydromorphone can produce: Common street names include: Severe respiratory depression, drowsiness • D, Dillies, Dust, Footballs, Juice, and Smack progressing to stupor or coma, lack of skeletal muscle tone, cold and clammy skin, constricted What does it look like? pupils, and reduction in blood pressure and heart Hydromorphone comes in: rate • Tablets, capsules, oral solutions, and injectable Severe overdose may result in death due to formulations respiratory depression. How is it abused? Which drugs cause similar effects? Users may abuse hydromorphone tablets by Drugs that have similar effects include: ingesting them. Injectable solutions, as well as • Heroin, morphine, hydrocodone, fentanyl, and tablets that have been crushed and dissolved oxycodone in a solution may be injected as a substitute for heroin. -
Opioid Receptorsreceptors
OPIOIDOPIOID RECEPTORSRECEPTORS defined or “classical” types of opioid receptor µ,dk and . Alistair Corbett, Sandy McKnight and Graeme Genes encoding for these receptors have been cloned.5, Henderson 6,7,8 More recently, cDNA encoding an “orphan” receptor Dr Alistair Corbett is Lecturer in the School of was identified which has a high degree of homology to Biological and Biomedical Sciences, Glasgow the “classical” opioid receptors; on structural grounds Caledonian University, Cowcaddens Road, this receptor is an opioid receptor and has been named Glasgow G4 0BA, UK. ORL (opioid receptor-like).9 As would be predicted from 1 Dr Sandy McKnight is Associate Director, Parke- their known abilities to couple through pertussis toxin- Davis Neuroscience Research Centre, sensitive G-proteins, all of the cloned opioid receptors Cambridge University Forvie Site, Robinson possess the same general structure of an extracellular Way, Cambridge CB2 2QB, UK. N-terminal region, seven transmembrane domains and Professor Graeme Henderson is Professor of intracellular C-terminal tail structure. There is Pharmacology and Head of Department, pharmacological evidence for subtypes of each Department of Pharmacology, School of Medical receptor and other types of novel, less well- Sciences, University of Bristol, University Walk, characterised opioid receptors,eliz , , , , have also been Bristol BS8 1TD, UK. postulated. Thes -receptor, however, is no longer regarded as an opioid receptor. Introduction Receptor Subtypes Preparations of the opium poppy papaver somniferum m-Receptor subtypes have been used for many hundreds of years to relieve The MOR-1 gene, encoding for one form of them - pain. In 1803, Sertürner isolated a crystalline sample of receptor, shows approximately 50-70% homology to the main constituent alkaloid, morphine, which was later shown to be almost entirely responsible for the the genes encoding for thedk -(DOR-1), -(KOR-1) and orphan (ORL ) receptors. -
Recommended Methods for the Identification and Analysis of Fentanyl and Its Analogues in Biological Specimens
Recommended methods for the Identification and Analysis of Fentanyl and its Analogues in Biological Specimens MANUAL FOR USE BY NATIONAL DRUG ANALYSIS LABORATORIES Laboratory and Scientific Section UNITED NATIONS OFFICE ON DRUGS AND CRIME Vienna Recommended Methods for the Identification and Analysis of Fentanyl and its Analogues in Biological Specimens MANUAL FOR USE BY NATIONAL DRUG ANALYSIS LABORATORIES UNITED NATIONS Vienna, 2017 Note Operating and experimental conditions are reproduced from the original reference materials, including unpublished methods, validated and used in selected national laboratories as per the list of references. A number of alternative conditions and substitution of named commercial products may provide comparable results in many cases. However, any modification has to be validated before it is integrated into laboratory routines. ST/NAR/53 Original language: English © United Nations, November 2017. All rights reserved. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. Mention of names of firms and commercial products does not imply the endorse- ment of the United Nations. This publication has not been formally edited. Publishing production: English, Publishing and Library Section, United Nations Office at Vienna. Acknowledgements The Laboratory and Scientific Section of the UNODC (LSS, headed by Dr. Justice Tettey) wishes to express its appreciation and thanks to Dr. Barry Logan, Center for Forensic Science Research and Education, at the Fredric Rieders Family Founda- tion and NMS Labs, United States; Amanda L.A. -
Fentanyl Infographic 24X36
FENTANYL WHAT IS IT? Fentanyl can be found in prescription form, introduced to the medical community in the 1960s Fentanyl analogues are now being Fentanyl is a potent synthetic and prescribed to relieve severe pain post-surgery created in clandestine laboratories to opioid analgesic, 50 to 100x or during end-of-life care . In its prescription form, be sold and used illegally. In it's non- more powerful than fentanyl is sold under the brand names Actiq®, prescription form, fentanyl is found in morphine. Duragesic®, and Sublimaze®. When prescribed by a powder form, spiked on blotter paper; physician, fentanyl is often administered via mixed with heroin; or as tablets that injection, transdermal patch, or in lozenges. attempt to mimic other opioids. Effects: Like other opioids, Fentanyl binds to Through Fentanyl's effects on the Euphoria, relaxation, drowsiness, opioid receptors in the reward centers opioid receptors in the brain stem nausea, confusion, constipation, of the brain, increasing dopamine however, it can inhibit normal sedation, tolerance, addiction, levels to cause a surge in endorphins breathing, causing breathing to stop respiratory depression and arrest, and feelings of pleasure. altogether, leading to death. unconsciousness, coma, and death. WHY DOES IT MATTER? 540% While the fast-acting nature of the effects of fentanyl may create a more powerful and immediate euphoria, these increase in fentanyl effects wear off faster, leading to the more immediate return overdose deaths of cravings and discomfort. since 2016 (CDC) With a high profit margin, Fentanyl is often mixed into heroin or is made to mimic the In talking about Fentanyl, you may hear about appearance of other opioids. -
Smoking and Pain Pathophysiology and Clinical Implications
REVIEW ARTICLE Anesthesiology 2010; 113:977–92 Copyright © 2010, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins Smoking and Pain Pathophysiology and Clinical Implications Yu Shi, M.D., M.P.H.,* Toby N. Weingarten, M.D.,† Carlos B. Mantilla, M.D., Ph.D.,‡ W. Michael Hooten, M.D.,† David O. Warner, M.D.§ ABSTRACT to deliver nicotine. Nicotine has analgesic properties, first Cigarette smoke, which serves as a nicotine delivery vehicle observed in feline visceral pain models3 and since then rep- in humans, produces profound changes in physiology. Ex- licated in numerous animal and human studies.4–13 Its anal- perimental studies suggest that nicotine has analgesic prop- gesic effects likely result from effects at both central and erties. However, epidemiologic evidence shows that smoking peripheral nicotine acetylcholine receptors (nAChRs).8,14,15 is a risk factor for chronic pain. The complex relationship Other nAChR ligands also have potent analgesic effects.16–20 between smoking and pain not only is of scientific interest, On the other hand, clinical evidence suggests that smokers but also has clinical relevance in the practice of anesthesiol- are at increased risk of developing back pain and other ogy and pain medicine. This review will examine current chronic pain disorders.21–32 Furthermore, comparisons be- knowledge regarding how acute and chronic exposure to nic- tween smokers and nonsmokers with chronic pain disorders otine and cigarette smoke affects acute and chronic painful have repeatedly demonstrated